Phage display allows de novo selection of ligands that bind to a large range of targets from libraries of polypeptides of great diversity (e.g., greater than 109 different polypeptides. Two important elements of selection in phage display makes phage display techniques of interest to researchers: (1) almost any peptide sequence can be displayed on the coat protein of phage by inserting a short DNA sequence into the genome of the phage and (2) bacteria infected by a phage displaying peptide produce multiple copies of this particular phage rapidly (e.g., amplification by ˜103 every 20-60 min).
Rounds of selection and amplification make it possible to select peptides from a phage display library that can bind usefully to targets. Modifications of phage coat proteins, however, can influence the rates of infection of bacteria, the rates of assembly of the new phage particles, and/or the rates of phage production from infected bacteria. When phage with different rates of amplification compete for the same pool of bacteria, clones that replicate more rapidly capture an increasing fraction of the total pool of bacteria, thereby reducing the diversity of the phage display library during amplification and thus, the usefulness of such amplified libraries. Accordingly, improvements in phage display and other amplification techniques are needed.